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Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance

Karine Alvarez 1 Jérôme Deval 1 Boulbaba Selmi 1 Karine Barral 1 Joelle Boretto 1 Catherine Guerreiro 2 Laurence Mulard 2 Robert Sarfati 2 Bruno Canard 1
1 AFMB - Architecture et fonction des Macromolécules Biologiques - UMR 6098
2 Chimie des Biomolécules - Chemistry of Biomolecules
Abstract : Alpha-boranophosphates suppress RT-mediated resistance when the catalytic rate of incorporation (kpol) of the analogue 5'-triphosphate is responsable for drug resistance, such as in the case of K65R mutant and ddNTPs, and Q151M toward AZTTP and ddNTPs. This suppression is also observed with BH3-d4T and BH3-3TC toward their clinically relevant mutants Q151M and M184V. Moreover, the presence of the borano (BH3-) group renders the incorporation of the analogue independent from amino-acid substitutions in RT. To our knowledge, this is the first example of rescue of polymerase activity by means of a nucleotide analogue
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Submitted on : Friday, March 8, 2019 - 11:47:27 AM
Last modification on : Friday, May 6, 2022 - 2:56:01 PM

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Karine Alvarez, Jérôme Deval, Boulbaba Selmi, Karine Barral, Joelle Boretto, et al.. Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance. Nucleosides, Nucleotides and Nucleic Acids, Taylor & Francis, 2005, 24 (5-7), pp.419-422. ⟨10.1081/NCN-200059951⟩. ⟨hal-02061659⟩

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